Search results for: STAT pathway
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 716

Search results for: STAT pathway

716 Induction of Apoptosis by Diosmin through Interleukins/STAT and Mitochondria Mediated Pathway in Hep-2 and KB Cells

Authors: M. Rajasekar, K. Suresh

Abstract:

Diosmin is a flavonoid, most abundantly found in many citrus fruits. As a flavonoid, it possesses a multitude of biological activities including anti-hyperglycemic, anti-lipid peroxidative, anti-inflammatory, antioxidant, and anti-mutagenic properties. At this point, we established the anti-proliferative and apoptosis-inducing activities of diosmin in Hep-2 and KB cells. Diosmin has cytotoxic effects through inhibiting cellular proliferation of Hep-2 and KB cells, which leads to the induction of apoptosis, as apparent by an increase in the fraction of cells in the sub-G1phase of the cell cycle. Results exposed that inhibition of cell proliferation is associated with regulation of the Interleukins/STAT pathway. In addition, Diosmin treatment with Hep-2 and KB cells actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. And also an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and shifting the balance in favor of apoptosis. These observations conclude that Diosmin induce apoptosis via Interleukins /STAT-mediated pathway.

Keywords: diosmin, apoptosis, antioxidant, STAT pathway

Procedia PDF Downloads 294
715 The Immunology Evolutionary Relationship between Signal Transducer and Activator of Transcription Genes from Three Different Shrimp Species in Response to White Spot Syndrome Virus Infection

Authors: T. C. C. Soo, S. Bhassu

Abstract:

Unlike the common presence of both innate and adaptive immunity in vertebrates, crustaceans, in particular, shrimps, have been discovered to possess only innate immunity. This further emphasizes the importance of innate immunity within shrimps in pathogenic resistance. Under the study of pathogenic immune challenge, different shrimp species actually exhibit varying degrees of immune resistance towards the same pathogen. Furthermore, even within the same shrimp species, different batches of challenged shrimps can have different strengths of immune defence. Several important pathways are activated within shrimps during pathogenic infection. One of them is JAK-STAT pathway that is activated during bacterial, viral and fungal infections by which STAT(Signal Transducer and Activator of Transcription) gene is the core element of the pathway. Based on theory of Central Dogma, the genomic information is transmitted in the order of DNA, RNA and protein. This study is focused in uncovering the important evolutionary patterns present within the DNA (non-coding region) and RNA (coding region). The three shrimp species involved are Macrobrachium rosenbergii, Penaeus monodon and Litopenaeus vannamei which all possess commercial significance. The shrimp species were challenged with a famous penaeid shrimp virus called white spot syndrome virus (WSSV) which can cause serious lethality. Tissue samples were collected during time intervals of 0h, 3h, 6h, 12h, 24h, 36h and 48h. The DNA and RNA samples were then extracted using conventional kits from the hepatopancreas tissue samples. PCR technique together with designed STAT gene conserved primers were utilized for identification of the STAT coding sequences using RNA-converted cDNA samples and subsequent characterization using various bioinformatics approaches including Ramachandran plot, ProtParam and SWISS-MODEL. The varying levels of immune STAT gene activation for the three shrimp species during WSSV infection were confirmed using qRT-PCR technique. For one sample, three biological replicates with three technical replicates each were used for qRT-PCR. On the other hand, DNA samples were important for uncovering the structural variations within the genomic region of STAT gene which would greatly assist in understanding the STAT protein functional variations. The partially-overlapping primers technique was used for the genomic region sequencing. The evolutionary inferences and event predictions were then conducted through the Bayesian Inference method using all the acquired coding and non-coding sequences. This was supplemented by the construction of conventional phylogenetic trees using Maximum likelihood method. The results showed that adaptive evolution caused STAT gene sequence mutations between different shrimp species which led to evolutionary divergence event. Subsequently, the divergent sites were correlated to the differing expressions of STAT gene. Ultimately, this study assists in knowing the shrimp species innate immune variability and selection of disease resistant shrimps for breeding purpose. The deeper understanding of STAT gene evolution from the perspective of both purifying and adaptive approaches not only can provide better immunological insight among shrimp species, but also can be used as a good reference for immunological studies in humans or other model organisms.

Keywords: gene evolution, JAK-STAT pathway, immunology, STAT gene

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714 IL6/PI3K/mTOR/GFAP Molecular Pathway Role in COVID-19-Induced Neurodegenerative Autophagy, Impacts and Relatives

Authors: Mohammadjavad Sotoudeheian

Abstract:

COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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713 Network Based Molecular Profiling of Intracranial Ependymoma over Spinal Ependymoma

Authors: Hyeon Su Kim, Sungjin Park, Hae Ryung Chang, Hae Rim Jung, Young Zoo Ahn, Yon Hui Kim, Seungyoon Nam

Abstract:

Ependymoma, one of the most common parenchymal spinal cord tumor, represents 3-6% of all CNS tumor. Especially intracranial ependymomas, which are more frequent in childhood, have a more poor prognosis and more malignant than spinal ependymomas. Although there are growing needs to understand pathogenesis, detailed molecular understanding of pathogenesis remains to be explored. A cancer cell is composed of complex signaling pathway networks, and identifying interaction between genes and/or proteins are crucial for understanding these pathways. Therefore, we explored each ependymoma in terms of differential expressed genes and signaling networks. We used Microsoft Excel™ to manipulate microarray data gathered from NCBI’s GEO Database. To analyze and visualize signaling network, we used web-based PATHOME algorithm and Cytoscape. We show HOX family and NEFL are down-regulated but SCL family is up-regulated in cerebrum and posterior fossa cancers over a spinal cancer, and JAK/STAT signaling pathway and Chemokine signaling pathway are significantly different in the both intracranial ependymoma comparing to spinal ependymoma. We are considering there may be an age-dependent mechanism under different histological pathogenesis. We annotated mutation data of each gene subsequently in order to find potential target genes.

Keywords: systems biology, ependymoma, deg, network analysis

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712 Dissolution of Zeolite as a Sorbent in Flue Gas Desulphurization Process Using a pH Stat Apparatus

Authors: Hilary Rutto, John Kabuba

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Sulphur dioxide is a harmful gaseous product that needs to be minimized in the atmosphere. This research work investigates the use of zeolite as a possible additive that can improve the sulphur dioxide capture in wet flue gas desulphurisation dissolution process. This work determines the effect of temperature, solid to liquid ratio, acid concentration and stirring speed on the leaching of zeolite using a pH stat apparatus. The atomic absorption spectrometer was used to measure the calcium ions from the solution. It was found that the dissolution rate of zeolite decreased with increase in solid to liquid ratio and increases with increase in temperature, stirring speed and acid concentration. The activation energy for the dissolution rate of zeolite in hydrochloric acid was found to be 9.29kJ/mol. and therefore the product layer diffusion was the rate limiting step.

Keywords: calcium ion, pH stat apparatus, wet flue gas desulphurization, zeolite

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711 Dissolution of South African Limestone for Wet Flue Gas Desulphurization

Authors: Lawrence Koech, Ray Everson, Hein Neomagus, Hilary Rutto

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Wet Flue gas desulphurization (FGD) systems are commonly used to remove sulphur dioxide from flue gas by contacting it with limestone in aqueous phase which is obtained by dissolution. Dissolution is important as it affects the overall performance of a wet FGD system. In the present study, effects of pH, stirring speed, solid to liquid ratio and acid concentration on the dissolution of limestone using an organic acid (adipic acid) were investigated. This was investigated using the pH stat apparatus. Calcium ions were analyzed at the end of each experiment using Atomic Absorption (AAS) machine.

Keywords: desulphurization, limestone, dissolution, pH stat apparatus

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710 A Novel Application of CORDYCEPIN (Cordycepssinensis Extract): Maintaining Stem Cell Pluripotency and Improving iPS Generation Efficiency

Authors: Shih-Ping Liu, Cheng-Hsuan Chang, Yu-Chuen Huang, Shih-Yin Chen, Woei-Cherng Shyu

Abstract:

Embryonic stem cells (ES) and induced pluripotnet stem cells (iPS) are both pluripotent stem cells. For mouse stem cells culture technology, leukemia inhibitory factor (LIF) was used to maintain the pluripotency of stem cells in vitro. However, LIF is an expensive reagent. The goal of this study was to find out a pure compound extracted from Chinese herbal medicine that could maintain stem cells pluripotency to replace LIF and improve the iPS generation efficiency. From 20 candidates traditional Chinese medicine we found that Cordycepsmilitaris triggered the up-regulation of stem cells activating genes (Oct4 and Sox2) expression levels in MEF cells. Cordycepin, a major active component of Cordycepsmilitaris, also could up-regulate Oct4 and Sox2 gene expression. Furthermore, we used ES and iPS cells and treated them with different concentrations of Cordycepin (replaced LIF in the culture medium) to test whether it was useful to maintain the pluripotency. The results showed higher expression levels of several stem cells markers in 10 μM Cordycepin-treated ES and iPS cells compared to controls that did not contain LIF, including alkaline phosphatase, SSEA1, and Nanog. Embryonic body formation and differentiation confirmed that 10 μM Cordycepin-containing medium was capable to maintain stem cells pluripotency after four times passages. For mechanism analysis, microarray analysis indicated extracellular matrix and Jak/Stat signaling pathway as the top two deregulated pathways. In ECM pathway, we determined that the integrin αVβ5 expression levels and phosphorylated Src levels increased after Cordycepin treatment. In addition, the phosphorylated Jak2 and phosphorylated Sat3 protein levels were increased after Cordycepin treatment and suppressed with the Jak2 inhibitor, AG490. The expression of cytokines associated with Jak2/Stat3 signaling pathway were also up-regulated by Q-PCR and ELISA assay. Lastly, we used Oct4-GFP MEF cells to test iPS generation efficiency following Cordycepin treatment. We observed that 10 Μm Cordycepin significantly increased the iPS generation efficiency in day 21. In conclusion, we demonstrated Cordycepin could maintain the pluripotency of stem cells through both of ECM and Jak2/Stat3 signaling pathway and improved iPS generation efficiency.

Keywords: cordycepin, iPS cells, Jak2/Stat3 signaling pathway, molecular biology

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709 Metabolomics Profile Recognition for Cancer Diagnostics

Authors: Valentina L. Kouznetsova, Jonathan W. Wang, Igor F. Tsigelny

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Metabolomics has become a rising field of research for various diseases, particularly cancer. Increases or decreases in metabolite concentrations in the human body are indicative of various cancers. Further elucidation of metabolic pathways and their significance in cancer research may greatly spur medicinal discovery. We analyzed the metabolomics profiles of lung cancer. Thirty-three metabolites were selected as significant. These metabolites are involved in 37 metabolic pathways delivered by MetaboAnalyst software. The top pathways are glyoxylate and dicarboxylate pathway (its hubs are formic acid and glyoxylic acid) along with Citrate cycle pathway followed by Taurine and hypotaurine pathway (the hubs in the latter are taurine and sulfoacetaldehyde) and Glycine, serine, and threonine pathway (the hubs are glycine and L-serine). We studied interactions of the metabolites with the proteins involved in cancer-related signaling networks, and developed an approach to metabolomics biomarker use in cancer diagnostics. Our analysis showed that a significant part of lung-cancer-related metabolites interacts with main cancer-related signaling pathways present in this network: PI3K–mTOR–AKT pathway, RAS–RAF–ERK1/2 pathway, and NFKB pathway. These results can be employed for use of metabolomics profiles in elucidation of the related cancer proteins signaling networks.

Keywords: cancer, metabolites, metabolic pathway, signaling pathway

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708 Impact of Crises on Official Statistics: Environmental Statistics at Statistical Centre for the Cooperation Council for the Arab Countries of the Gulf during the COVID-19 Pandemic: A Case Study

Authors: Ibtihaj Al-Siyabi

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The crisis of COVID-19 posed enormous challenges to the statistical providers. While official statistics were disrupted by the pandemic and related containment measures, there was a growing and pressing need for real-time data and statistics to inform decisions. This paper gives an account of the way the pandemic impacted the operations of the National Statistical Offices (NSOs) in general in terms of data collection and methods used and the main challenges encountered by them based on international surveys. It highlights the performance of the Statistical Centre for the Cooperation Council for the Arab Countries of the Gulf, GCC-STAT, and its responsiveness to the pandemic placing special emphasis on environmental statistics. The paper concludes by confirming the GCC-STAT’s resilience and success in facing the challenges.

Keywords: NSO, COVID-19, statistics, crisis, pandemic

Procedia PDF Downloads 91
707 Leaching of Copper from Copper Ore Using Sulphuric Acid in the Presence of Hydrogen Peroxide as an Oxidizing Agent: An Optimized Process

Authors: Hilary Rutto

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Leaching with acids are the most commonly reagents used to remove copper ions from its copper ores. It is important that the process conditions are optimized to improve the leaching efficiency. In the present study the effects of pH, oxidizing agent (hydrogen peroxide), stirring speed, solid to liquid ratio and acid concentration on the leaching of copper ions from it ore were investigated using a pH Stat apparatus. Copper ions were analyzed at the end of each experiment using Atomic Absorption (AAS) machine. Results showed that leaching efficiency improved with an increase in acid concentration, stirring speed, oxidizing agent, pH and decreased with an increase in the solid to liquid ratio.

Keywords: leaching, copper, oxidizing agent, pH stat apparatus

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706 Reactivity Study on South African Calcium Based Material Using a pH-Stat and Citric Acid: A Statistical Approach

Authors: Hilary Rutto, Mbali Chiliza, Tumisang Seodigeng

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The study on reactivity of calcined calcium-based material is very important in dry flue gas desulphurisation (FGD) process, so as to produce absorbent with high sulphur dioxide capture capacity during the hydration process. The effect of calcining temperature and time on the reactivity of calcined limestone material were investigated. In this study, the reactivity was measured using a pH stat apparatus and also confirming the result by performing citric acid reactivity test. The reactivity was calculated using the shrinking core model. Based on the experiments, a mathematical model is developed to correlate the effect of time and temperature to the reactivity of absorbent. The calcination process variables were temperature (700 -1000°C) and time (1-6 hrs). It was found that reactivity increases with an increase in time and temperature.

Keywords: reactivity, citric acid, calcination, time

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705 Recognition of Gene Names from Gene Pathway Figures Using Siamese Network

Authors: Muhammad Azam, Micheal Olaolu Arowolo, Fei He, Mihail Popescu, Dong Xu

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The number of biological papers is growing quickly, which means that the number of biological pathway figures in those papers is also increasing quickly. Each pathway figure shows extensive biological information, like the names of genes and how the genes are related. However, manually annotating pathway figures takes a lot of time and work. Even though using advanced image understanding models could speed up the process of curation, these models still need to be made more accurate. To improve gene name recognition from pathway figures, we applied a Siamese network to map image segments to a library of pictures containing known genes in a similar way to person recognition from photos in many photo applications. We used a triple loss function and a triplet spatial pyramid pooling network by combining the triplet convolution neural network and the spatial pyramid pooling (TSPP-Net). We compared VGG19 and VGG16 as the Siamese network model. VGG16 achieved better performance with an accuracy of 93%, which is much higher than OCR results.

Keywords: biological pathway, image understanding, gene name recognition, object detection, Siamese network, VGG

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704 Biomarkers, A Reliable Tool for Delineating Spill Trajectory

Authors: Okpor Victor, Selegha Abrakasa

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Oil (Petroleum) spill occur frequently and in this era of a higher degree of awareness, it is pertinent that the trajectory of the spill is properly defined, to make certain of the area of impact by the spill. In this study, biomarkers that are known as the custodians of paleo information in oils are suggested to be used as reliable tools for defining the pathway of a spill. Samples were collected as tills alongside the GPS coordinates of the sample points suspected to have been impacted by a spill. Oils in the samples were extracted and analyzed as whole oil using GC–MS. Some biomarker parametric ratios were derived, and the ratio showed consistency of values along the sample trail from sample 1 to sample 20. The consistency of the values indicates that the oils at each sample point are the same hence the same value. This method can be used to validate the trajectory/pathway of a spill and also to define or establish a suspected pathway for a spill. The Oleanane/C30Hopane ratio showed good consistency and was suggested as a reliable parameter for establishing the trajectory of an oil spill.

Keywords: spill, biomarkers, trajectory, pathway

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703 Competition Between the Effects of Pesticides and Immune-activation on the Expression of Toll Pathway Genes

Authors: Dani Sukkar, Ali Kanso, Philippe Laval-Gilly, Jairo Falla-Angel

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The honeybees' immune system is challenged by different risk factors that induce various responses. However, complex scenarios where bees are exposed to different pesticides simultaneously with immune activation are not well evaluated. The Toll pathway is one of the main signaling pathways studied in invertebrate immune responses, and it is a good indicator of the effect of such complex interactions in addition to key signaling elements of other pathways like Relish of the immune deficiency (IMD) pathway or Eater, the phagocytosis receptor or vitellogenin levels. Honeybee hemocytes extracted from 5th instar larvae were exposed to imidacloprid and/or amitraz with or without the presence of the zymosan a as an immune activator. The gene expression of multiple immune related genes were studied, including spaetzle, Toll, myD88, relish, eater and vitellogenin, by real-time polymerase chain reaction after RNA extraction. The results demonstrated that the Toll pathway is mainly affected by the pesticides; imidacloprid and amitraz, especially by their different combinations. Furthermore, immune activation by zymosan A, a fungal cell-wall component, acts to mitigate to some extent the effect of pesticides on the different levels of the Toll pathway. In addition, imidacloprid, amitraz, and zymosan A have complex and context-specific interactions depending on the levels of immune activation and the pathway evaluated affecting immune-gene expression differently.

Keywords: toll pathway, immune modulation, β-glucan, imidacloprid, amitraz, honeybees, immune genes

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702 Clinical Pathway for Postoperative Organ Transplants

Authors: Tahsien Okasha

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Transplantation medicine is one of the most challenging and complex areas of modern medicine. Some of the key areas for medical management are the problems of transplant rejection, during which the body has an immune response to the transplanted organ, possibly leading to transplant failure and the need to immediately remove the organ from the recipient. When possible, transplant rejection can be reduced through serotyping to determine the most appropriate donor-recipient match and through the use of immunosuppressant drugs. Postoperative care actually begins before the surgery in terms of education, discharge planning, nutrition, pulmonary rehabilitation, and patient/family education. This also allows for expectations to be managed. A multidisciplinary approach is the key, and collaborative team meetings are essential to ensuring that all team members are "on the same page.". The following clinical pathway map and guidelines with the aim to decrease alteration in clinical practice and are intended for those healthcare professionals who look after organ transplant patients. They are also intended to be useful to both medical and surgical trainees as well as nurse specialists and other associated healthcare professionals involved in the care of organ transplant patients. This pathway is general pathway include the general guidelines that can be applicable for all types of organ transplant with special considerations to each organ.

Keywords: organ transplant, clinical pathway, postoperative care, same page

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701 Clinical Pathway for Postoperative Organ Transplantation

Authors: Tahsien Okasha

Abstract:

Transplantation medicine is one of the most challenging and complex areas of modern medicine. Some of the key areas for medical management are the problems of transplant rejection, during which the body has an immune response to the transplanted organ, possibly leading to transplant failure and the need to immediately remove the organ from the recipient. When possible, transplant rejection can be reduced through serotyping to determine the most appropriate donor-recipient match and through the use of immunosuppressant drugs. Postoperative care actually begins before the surgery in terms of education, discharge planning, nutrition, pulmonary rehabilitation, and patient/family education. This also allows for expectations to be managed. A multidisciplinary approach is the key, and collaborative team meetings are essential to ensuring that all team members are "on the same page." .The following clinical pathway map and guidelines with the aim to decrease alteration in clinical practice and are intended for those healthcare professionals who look after organ transplant patients. They are also intended to be useful to both medical and surgical trainees as well as nurse specialists and other associated healthcare professionals involved in the care of organ transplant patients. This pathway is general pathway include the general guidelines that can be applicable for all types of organ transplant with special considerations to each organ.

Keywords: postoperative care, organ transplant, clinical pathway, patient

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700 Analysis of the Transcriptional Response of Rhazia stricta to Jasmonic Acid Induction

Authors: Nahid H. Hajrah, Jamal S. M. Sabir, Neil Hall

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The jasmonic pathway is ubiquitous in plants and is crucial to plant development. It Is involved in fertility, ripening, and sex determination as well as in response to environmental stresses such as herbivory, pathogen drought or temperature shock. Essentially the jasmonic pathway acts to shut down growth in order to induce defence pathways. These pathways include the production of secondary metabolites which have evolved to defend against herbivores and pathogens but are of increasing interest due to their roll in medicine and biotechnology. Here we describe the transcriptional response of Rhazia stricta (a poisonous shrub widely used in traditional medicine) to jasmonic acid, in order to better characterize the genes involved in secondary metabolite production and its response to stress. We observe coordinated upregulation of flavonoid biosynthesis pathway leading to flavonols, flavones and anthocyanins but no similar coordination of the monoterpene indole alkaloid pathway.

Keywords: medicinal plants, Rhazia stricta, jasmonic acid, transcriptional analysis

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699 Pathway and Differential Gene Expression Studies for Colorectal Cancer

Authors: Ankita Shukla, Tiratha Raj Singh

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Colorectal cancer (CRC) imposes serious mortality burden worldwide and it has been increasing for past consecutive years. Continuous efforts have been made so far to diagnose the disease condition and to identify the root cause for it. In this study, we performed the pathway level as well as the differential gene expression studies for CRC. We analyzed the gene expression profile GSE24514 from Gene Expression Omnibus (GEO) along with the gene pathways involved in the CRC. This analysis helps us to understand the behavior of the genes that have shown differential expression through their targeted pathways. Pathway analysis for the targeted genes covers the wider area which therefore decreases the possibility to miss the significant ones. This will prove to be beneficial to expose the ones that have not been given attention so far. Through this analysis, we attempt to understand the various neighboring genes that have close relationship to the targeted one and thus proved to be significantly controlling the CRC. It is anticipated that the identified hub and neighboring genes will provide new directions to look at the pathway level differently and will be crucial for the regulatory processes of the disease.

Keywords: mismatch repair, microsatellite instability, carcinogenesis, morbidity

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698 The Retinoprotective Effects and Mechanisms of Fungal Ingredient 3,4-Dihydroxybenzalacetone through Inhibition of Retinal Müller and Microglial Activation

Authors: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

Abstract:

Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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697 A Risk Pathway of Distal and Proximal Factors for Self-Injury among Adolescents

Authors: Sarit Gideoni Cohen

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The aim of the study was to examine possible risk pathway which initiated by the distal risk factors of insecure attachment to the mother, the father and peers and then developed by means of proximal risk factors: stressful life events and emotional distress. 275 participants (aged 13-26) from high-schools, youth groups and university were requited. Twenty-two percent participants reported at least one episode of self-injury. The relationship between paternal and peer attachment were partly mediated by stressful life events and depressive symptoms. Paternal and peer attachment influences during adolescence as contributing to risk pathway for self-injury were acknowledged.

Keywords: self-injury, attachment, depression, stressful life-events, adolescence

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696 Identification of Tissue-Specific Transcription Factors in C. roseus with Emphasis to the TIA Biosynthetic Pathway

Authors: F. M. El-Domyati, A. Atef, S. Edris, N. O. Gadalla, M. A. Al-Kordy, A. M. Ramadan, Y. M. Saad, H. S. Al-Zahrani, A. Bahieldin

Abstract:

Transcriptome retrieved from SRA database of different tissues and treatments of C. roseus was assembled in order to detect tissue-specific transcription factors (TFs) and TFs possibly related to terpenoid indole alkaloids (TIA) pathway. A number of 290 TF-like transcripts along with 12 transcripts related to TIA biosynthetic pathway were divided in terms of co-expression in the different tissues, treatments and genotypes. Three transcripts encoding peroxidases 1 and 12 were downregulated in hairy root, while upregulated in mature leaf. Eight different transcripts of the TIA pathway co-expressed with TFs either functioning downstream tryptophan biosynthesis, e.g., tdc, str1 and sgd, or upstream vindoline biosynthesis, e.g., t16h, omt, nmt, d4h and dat. The results showed no differential expression of TF transcripts in hairy roots knocked down for tdc gene (TDCi) as compared to their wild type controls. There were several evidences of tissue-specific expression of TF transcripts in flower, mature leaf, root/hairy root, stem, seedling, hairy root and immature/mature leaves. Regulation included transcription factor families, e.g., bHLH, MYB and WRKY mostly induced by ABA and/or JA (or MeJA) and regulated during abiotic or biotic stress. The information of tissue-specific regulation and co-expression of TFs and genes in the TIA pathway can be utilized in manipulating alkaloid biosynthesis in C. roseus.

Keywords: SRA database, bHLH, MYB, WRKY, co-expression

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695 Auricular Electroacupuncture Rescued Epilepsy Seizure by Attenuating TLR-2 Inflammatory Pathway in the Kainic Acid-Induced Rats

Authors: I-Han Hsiao, Chun-Ping Huang, Ching-Liang Hsieh, Yi-Wen Lin

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Epilepsy is chronic brain disorder that results in the sporadic occurrence of spontaneous seizures in the temporal lobe, cerebral cortex, and hippocampus. Clinical antiepileptic medicines are often ineffective or little benefits in the small amount of patients and usually initiate severe side effects. This inflammation contributes to enhanced neuronal excitability and the onset of epilepsy. Auricular electric-stimulation (AES) can increase parasympathetic activity and stimulate the solitary tract nucleus to induce the cholinergic anti-inflammatory pathway. Furthermore, it may be a therapeutic strategy for the treatment of epilepsy. In the present study, we want to investigate the effects of AES on inflammatory mediators in kainic acid (KA)-induced epileptic seizure rats. Experimental KA injection increased expression of TLR-2 pathway associated inflammatory mediators, were further reduced by either 2Hz or 15 Hz AES in the prefrontal cortex, hippocampus, and somatosensory cortex. We suggest that AES can successfully control the epileptic seizure by down-regulation of inflammation signaling pathway.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation

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694 Application of KL Divergence for Estimation of Each Metabolic Pathway Genes

Authors: Shohei Maruyama, Yasuo Matsuyama, Sachiyo Aburatani

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The development of the method to annotate unknown gene functions is an important task in bioinformatics. One of the approaches for the annotation is The identification of the metabolic pathway that genes are involved in. Gene expression data have been utilized for the identification, since gene expression data reflect various intracellular phenomena. However, it has been difficult to estimate the gene function with high accuracy. It is considered that the low accuracy of the estimation is caused by the difficulty of accurately measuring a gene expression. Even though they are measured under the same condition, the gene expressions will vary usually. In this study, we proposed a feature extraction method focusing on the variability of gene expressions to estimate the genes' metabolic pathway accurately. First, we estimated the distribution of each gene expression from replicate data. Next, we calculated the similarity between all gene pairs by KL divergence, which is a method for calculating the similarity between distributions. Finally, we utilized the similarity vectors as feature vectors and trained the multiclass SVM for identifying the genes' metabolic pathway. To evaluate our developed method, we applied the method to budding yeast and trained the multiclass SVM for identifying the seven metabolic pathways. As a result, the accuracy that calculated by our developed method was higher than the one that calculated from the raw gene expression data. Thus, our developed method combined with KL divergence is useful for identifying the genes' metabolic pathway.

Keywords: metabolic pathways, gene expression data, microarray, Kullback–Leibler divergence, KL divergence, support vector machines, SVM, machine learning

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693 Alleviation of Endoplasmic Reticulum Stress in Mosquito Cells to Survive Dengue 2 Virus Infection

Authors: Jiun-Nan Hou, Tien-Huang Chen, Wei-June Chen

Abstract:

Dengue viruses (DENVs) are naturally transmitted between humans by mosquito vectors. Mosquito cells usually survive DENV infection, allowing infected mosquitoes to retain an active status for virus transmission. In this study, we found that DENV2 virus infection in mosquito cells causes the unfolded protein response (UPR) that activates the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signal pathway, leading to shutdown of global protein translation in infected cells which was apparently regulated by the PERK signal pathway. According to observation in this study, the PERK signal pathway in DENV2-infected C6/36 cells alleviates ER stress, and reduces initiator and effector caspases, as well as the apoptosis rate via shutdown of cellular proteins. In fact, phosphorylation of eukaryotic initiation factor 2ɑ (eIF2ɑ) by the PERK signal pathway may impair recruitment of ribosomes that bind to the mRNA 5’-cap structure, resulting in an inhibitory effect on canonical cap-dependent cellular protein translation. The resultant pro-survival “byproduct” of infected mosquito cells is undoubtedly advantageous for viral replication. This finding provides insights into elucidating the PERK-mediated modulating web that is actively involved in dynamic protein synthesis, cell survival, and viral replication in mosquito cells.

Keywords: cap-dependent protein translation, dengue virus, endoplasmic reticulum stress, mosquito cells, PERK signal pathway

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692 Gene Names Identity Recognition Using Siamese Network for Biomedical Publications

Authors: Micheal Olaolu Arowolo, Muhammad Azam, Fei He, Mihail Popescu, Dong Xu

Abstract:

As the quantity of biological articles rises, so does the number of biological route figures. Each route figure shows gene names and relationships. Annotating pathway diagrams manually is time-consuming. Advanced image understanding models could speed up curation, but they must be more precise. There is rich information in biological pathway figures. The first step to performing image understanding of these figures is to recognize gene names automatically. Classical optical character recognition methods have been employed for gene name recognition, but they are not optimized for literature mining data. This study devised a method to recognize an image bounding box of gene name as a photo using deep Siamese neural network models to outperform the existing methods using ResNet, DenseNet and Inception architectures, the results obtained about 84% accuracy.

Keywords: biological pathway, gene identification, object detection, Siamese network

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691 Acute Respiratory Distress Syndrome (ARDS) Developed Clinical Pathway: Suggested Protocol

Authors: Maha Salah, Hanaa Hashem, Mahmoud M. Alsagheir, Mohammed Salah

Abstract:

Acute respiratory distress syndrome (ARDS) represents a complex clinical syndrome and carries a high risk for mortality. The severity of the clinical course, the uncertainty of the outcome, and the reliance on the full spectrum of critical care resources for treatment mean that the entire health care team is challenged. Researchers and clinicians have investigated the nature of the pathological process and explored treatment options with the goal of improving outcome. Through this application of research to practice, we know that some previous strategies have been ineffective, and innovations in mechanical ventilation, sedation, nutrition, and pharmacological intervention remain important research initiatives. Developed Clinical pathway is multidisciplinary plans of best clinical practice for this specified groups of patients that aid in the coordination and delivery of high quality care. They are a documented sequence of clinical interventions that help a patient to move, progressively through a clinical experience to a desired outcome. Although there is a lot of heterogeneity in patients with ARDS, this suggested developed clinical pathway with alternatives was built depended on a lot of researches and evidence based medicine and nursing practices which may be helping these patients to improve outcomes, quality of life and decrease mortality.

Keywords: acute respiratory distress syndrome (ARDS), clinical pathway, clinical syndrome

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690 Microbial Bioproduction with Design of Metabolism and Enzyme Engineering

Authors: Tomokazu Shirai, Akihiko Kondo

Abstract:

Technologies of metabolic engineering or synthetic biology are essential for effective microbial bioproduction. It is especially important to develop an in silico tool for designing a metabolic pathway producing an unnatural and valuable chemical such as fossil materials of fuel or plastics. We here demonstrated two in silico tools for designing novel metabolic pathways: BioProV and HyMeP. Furthermore, we succeeded in creating an artificial metabolic pathway by enzyme engineering.

Keywords: bioinformatics, metabolic engineering, synthetic biology, genome scale model

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689 Neuroprotective Effect of Tangeretin against Potassium Dichromate-Induced Acute Brain Injury via Modulating AKT/Nrf2 Signaling Pathway in Rats

Authors: Ahmed A. Sedik, Doaa Mahmoud Shuaib

Abstract:

Brain injury is a cause of disability and death worldwide. Potassium dichromate (PD) is an environmental contaminant widely recognized as teratogenic, carcinogenic, and mutagenic towards animals and humans. The aim of the present study was to investigate the possible neuroprotective effects of tangeretin (TNG) on PD-induced brain injury in rats. Forty male adult Wistar rats were randomly and blindly allocated into four groups (8 rats /group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. Four groups received TNG (100 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. 18- hours after the final treatment, behavioral parameters, neuro-biochemical indices, FTIR analysis, and histopathological studies were evaluated. Results of the present study revealed that rats intoxicated with PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in Nrf2 signaling pathway and GSH levels with an increase in brain contents of TNF-α, IL-10, and NF-kβ and reduced AKT levels in brain homogenates. Treatment with TNG (100 mg/kg; orally) ameliorated behavioral, cholinergic activities and oxidative stress, decreased the elevated levels of pro-inflammatory mediators; TNF-α, IL-10, and NF-κβ elevated AKT pathway with corrected FTIR spectra with a decrease in brain content of chromium residues detected by atomic absorption spectrometry. Also, TNG administration restored the morphological changes as degenerated neurons and necrosis associated with PD intoxication. Additionally, TNG decreased Caspase-3 expression in the brain of PD rats. TNG plays a crucial role in AKT/Nrf2 pathway that is responsible for their antioxidant, anti-inflammatory effects, and apoptotic pathway against PD-induced brain injury in rats.

Keywords: tangeretin, potassium dichromate, brain injury, AKT/Nrf2 signaling pathway, FTIR, atomic absorption spectrometry

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688 Sulforaphane Attenuates Muscle Inflammation in Dystrophin-Deficient Mdx Mice via Nrf2/HO-1 Signaling Pathway

Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

Abstract:

Backgrounds: Inflammation is widely distributed in patients with Duchenne muscular dystrophy (DMD), and ultimately leads to progressive deterioration of muscle function with the co-effects of chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzymes, heme oxygenase-1 (HO-1). However, whether Nrf2/HO-1 pathway can attenuate muscle inflammation on DMD remains unknown. The purpose of this study was to determine the anti-inflammatory effects of Sulforaphane (SFN) on DMD. Methods: 4-week-old male mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 4 weeks. Gastrocnemius, tibial anterior and triceps brachii muscles were collected for related analysis. Immune cell infiltration in skeletal muscles was analyzed by H&E staining and immuno-histochemistry. Moreover, the expressions of inflammatory cytokines,pro-inflammatory cytokines and Nrf2/HO-1 pathway were detected by western blot, qRT-PCR, immunohistochemistry and immunofluorescence assays. Results: Our results demonstrated that SFN treatment increased the expression of muscle phase II enzymes HO-1 in Nrf2 dependent manner. Inflammation in mdx skeletal muscles was reduced by SFN treatment as indicated by decreased immune cell infiltration and lower expressions of the inflammatory cytokines CD45, pro-inflammatory cytokines tumour necrosis factor-α and interleukin-6 in the skeletal muscles of mdx mice. Conclusions: Collectively, these results show that SFN can ameliorate muscle inflammation in mdx mice by Nrf2/HO-1 pathway, which indicates Nrf2/HO-1 pathway may represent a new therapeutic target for DMD.

Keywords: sulforaphane, Nrf2, HO-1, inflammation

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687 A New Development Pathway And Innovative Solutions Through Food Security System

Authors: Osatuyi Kehinde Micheal

Abstract:

There is much research that has contributed to an improved understanding of the future of food security, especially during the COVID-19 pandemic. A pathway was developed by using a local community kitchen in Muizenberg in western cape province, cape town, south Africa, a case study to map out the future of food security in times of crisis. This kitchen aims to provide nutritious, affordable, plant-based meals to our community. It is also a place of diverse learning, sharing, empowering the volunteers, and growth to support the local economy and future resilience by sustaining our community kitchen for the community. This document contains an overview of the story of the community kitchen on how we create self-sustainability as a new pathway development to sustain the community and reduce Zero hunger in the regional food system. This paper describes the key elements of how we respond to covid-19 pandemic by sharing food parcels and creating 13 soup kitchens across the community to tackle the immediate response to covid-19 pandemic and agricultural systems by growing home food gardening in different homes, also having a consciousness Dry goods store to reduce Zero waste and a local currency as an innovation to reduce food crisis. Insights gained from our article and outreach and their value in how we create adaptation, transformation, and sustainability as a new development pathway to solve any future problem crisis in the food security system in our society.

Keywords: sustainability, food security, community development, adapatation, transformation

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